Oral melanotic macule and primary oral malignant melanoma

Oral melanotic macule and primary oral malignant melanoma:
Epidemiology, location involved, and clinical implications
Zheng-Yu Shen, MD,a Wei Liu, MD,b Zhe-Xuan Bao, DDS,b Zeng-Tong Zhou, DDS,b and
Li-Zhen Wang, DDS,c Shanghai, China
NINTH PEOPLE’S HOSPITAL, SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE
Background. Oral malignant melanoma must be differentiated from melanotic macule.
Study design. Retrospective review of 2 series of oral melanotic macule (n ⫽ 52) and oral melanoma (n ⫽ 130) were
conducted to investigate the epidemiology and location involved and assess their differences.
Results. The mean age of oral melanotic macule patients was 47.3 years, with female:male ratio 2.1 and the lower lip
being the predominant location. The mean age of oral melanoma patients was 53.8 years, with no observed sex
predilection and the main locations being palate and gingiva. Differences between the 2 cohorts in age (P ⫽ .006),
gender (P ⫽ .014), and lesion site (P ⬍ .001) were noted. In this review, 1 case of oral melanotic macule was found to
subsequently develop into melanoma.
Conclusions. Oral melanotic macule may possess malignant potential. Biopsy is recommended to differentiate oral
melanoma from melanotic macule for male patients ⬎60 years old with suspected melanotic macule lesion located on
the palate. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:e21-e25)
Oral melanotic macule and primary oral malignant melanoma are 2 clinically and histologically distinctive
oral pigmented lesions.1 Oral melanotic macule usually
is a small well circumscribed and brown-to-black flat
macule that occurs on the lip and mucous membranes,
with an increase in melanin deposition in the basal cell
layer of the epithelium. Kahn et al. described a case of
benign melanotic macule developing into primary oral
malignant melanoma in the follow-up period,2 yet oral
melanotic macule is traditionally known to be a benign
pigmented lesion with no malignant potential.3-6 This
apparent discrepancy presents an academic and clinical
challenge.
Oral malignant melanoma is a malignant neoplasm
of melanocytes or of melanocyte precursors and is
characterized by proliferation of atypical melanocytes
at the epithelial connective tissue interface.7 It is exceedingly rare, representing ⬍1% of all melanomas and
only ⬃0.5% of oral malignancies.8-14 Oral melanoma is
Supported by the State Administration of Traditional Chinese Medicine of China (09J1X1L420B227), Science and Technology Commission of Shanghai (08DZ2271100 and 10DZ1974200) and Shanghai Leading Academic Discipline Project (S30206).
The first 2 authors contributed equally to this work.
a
Department of Dermatology, Ninth People’s Hospital.
b
Department of Oral Mucosal Diseases..
c
Department of Oral Pathology..
Received for publication Nov. 1, 2010; returned for revision Feb. 21,
2011; accepted for publication Feb. 28, 2011.
1079-2104/$ - see front matter
Crown Copyright © 2011 Published by Mosby, Inc. All rights
reserved.
doi:10.1016/j.tripleo.2011.02.040
known to behave aggressively, often with extremely
poor prognosis, e.g., a 5-year survival rate of 10%25%.8-13 The poor clinical outcome is partly due to
patients’ failure to recognize signs of early lesion and
physicians’ delayed diagnoses, resulting in frequent
diagnoses at advanced stage.
Oral malignant melanoma must be differentiated
from other oral benign pigmented lesions. Clinically,
oral melanoma is usually asymptomatic in the early
stage and presents normally as a flat pigmented lesion
or as a mass with a rapid growth rate.15 Meleti et al.16
reported a retrospective analysis of the presence of an
oral melanocytic nevus without an increased risk of oral
melanoma development. Unfortunately, there are no
striking features to distinguish oral melanoma from
other oral pigmented lesions. No reports comparing
series of oral melanotic macule or melanoma have been
found in literature from China, and information on the
clinical profiles regarding these is missing. We therefore retrospectively reviewed 2 series of oral melanotic
macule (n ⫽ 52) and oral malignant melanoma (n ⫽
130) from China to investigate the epidemiologic features and locations involved and to estimate the differences of the patients of the 2 groups in a hospital-based
study.
MATERIALS AND METHODS
All the medical records of patients with the clinical
and pathologic diagnosis of oral melanotic macule and
melanoma from 1993 to 2009 in a standard computerized database of Ninth People’s Hospital, Shanghai Jiao
Tong University School of Medicine, were retrieved
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Shen et al.
Table I. Baseline characteristics of oral melanotic macule, n (%)
Patients
Age, y
Mean (SD)
Range
⬍40
40-49
50-59
ⱖ60
Site
Lower lip
Gingiva
Buccal
mucosa
Palate
Upper lip
Tongue
Total
Male
Female
52
17
35
47.3 (13.9)
20-75
16 (30.8)
10 (19.2)
17 (32.7)
9 (17.3)
50.9 (15.6)
21-72
3 (17.6)
5 (29.4)
3 (17.6)
6 (35.3)
45.5 (12.8)
20-75
13 (37.1)
5 (14.3)
14 (40.0)
3 (8.6)
19 (36.5)
14 (26.9)
9 (17.3)
7 (41.2)
3 (17.6)
4 (23.5)
12 (34.3)
11 (31.4)
5 (14.3)
7 (13.5)
2 (3.8)
1 (1.9)
2 (11.8)
1 (5.9)
—
5 (14.3)
1 (2.9)
1 (2.9)
and retrospectively reviewed. Histopathologic diagnosis of oral melanotic macule and melanoma were confirmed by the oral pathologists from hematoxylin-eosin–stained slides. Diagnosis of oral melanotic macule
and primary oral melanoma were made based on criteria recommended in published literature.7,17 Information regarding age, gender, and site of lesions were all
documented in detail. A case-control analysis of oral
melanotic macule and melanoma was performed. This
study was approved by the Institutional Review Board.
The statistical differences between the melanotic macule and melanoma cohorts was assessed. Differences
in age were assessed by using the Student t test. Differences in age group and site of lesions were measured
by using the nonparametric test. The ␹2 test was used to
assess the association among gender. All tests were 2
sided, and P values of ⬍.05 were considered to be
statistically significant.
RESULTS
Characteristics of oral melanotic macule. The baseline characteristics of oral melanotic macule are presented in Table I. A total of 52 patients with melanotic
macule were identified for this study, ranging from 20
to 75 years in age with an average age was 47.3 years
at the time of diagnosis. There were 17 men and 35
women (M:F ratio 1:2.1). The peaks of age-frequency
distribution were the fifth decade for women (40.0%)
and after the sixth decade for men (35.3%). Lower lip
(36.5%) was the main location involved.
Characteristics of oral malignant melanoma. The
baseline characteristics of oral melanoma are shown in
Table II. A total of 130 patients with melanoma were
identified for the present study, ranging from 3 to 90
Table II. Baseline characteristics of primary oral malignant melanoma, n (%)
Patients
Age, y
Mean (SD)
Range
⬍40
40-49
50-59
ⱖ60
Site
Palate
Gingiva
Maxilla
Buccal
mucosa
Mandible
Tongue
Upper lip
Lower lip
Multiple
Total
Male
Female
130
69
61
53.8 (14.4)
3-90
21 (16.2)
26 (20.0)
39 (30.0)
44 (33.8)
53.3 (14.6)
3-84
11 (15.9)
18 (26.1)
18 (26.1)
22 (31.9)
54.5 (14.4)
20-90
10 (16.4)
8 (13.1)
21 (34.4)
22 (36.1)
52 (40.0)
52 (40.0)
11 (8.5)
6 (4.6)
26 (37.7)
28 (40.5)
4 (5.8)
4 (5.8)
26 (42.6)
24 (39.4)
7 (11.5)
2 (3.3)
3 (2.3)
1 (0.8)
1 (0.8)
2 (1.5)
2 (1.5)
3 (4.3)
1 (1.4)
1 (1.4)
1 (1.4)
1 (1.4)
—
—
—
1 (1.6)
1 (1.6)
years old, with the average age at the time of diagnosis
of 53.8 years. There were 69 male and 61 female
patients with a male-to-female ratio of 1.1:1. There was
no difference in age distribution between male and
female. The highest incidence occurred in the sixth
decade of life for both genders. Palate and gingiva were
affected in 52 (40.0%) and 52 (40.0%) cases, respectively.
Comparative analysis of oral melanotic macule and
melanoma. To define the differences of clinical parameters between oral melanotic macule and melanoma, a
comparative analysis was performed (Table III). The
mean age of the patients with melanotic macule was
47.3 years old compared with 53.8 years with melanoma (Student t test: P ⫽ .006), with a difference in the
age group (⬍40 years, 40-59 years, ⱖ60 years; nonparametric test: P ⫽ .007). Significant differences in
gender (␹2 test: P ⫽ .014) and site of lesion (nonparametric test: P ⬍ .001) were also observed between the
2 groups.
Patients with oral melanotic macule and melanoma
association. We found 3 associated cases of oral melanotic macule and melanoma. Case 1 (a 60-year-old
woman) was diagnosed with an oral melanotic macule
at the palate by biopsy. After 1 month, diagnosis of
melanoma was made at the same area of the palate (Fig.
1). Case 2 (a 60-year-old woman) was diagnosed with
oral melanotic macule concomitant melanoma at the
palate (Fig. 2). Case 3 (a 72-year-old man) underwent
the first surgical excision with a diagnosis of oral melanoma at the lower lip. After 29 months, he had the
second surgical excision and was diagnosed with a
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Table III. Comparison of oral melanotic macule and
melanoma
Patients
Age, y
Mean
(SD)
Range
Age group, y
⬍40
40-59
ⱖ60
Gender
Female
Male
Site
Lip
Gingiva
Palate
Melanotic macule
Melanoma
52
130
47.3 (13.9)
53.8 (14.4)
20–75
3–90
P value
.006
.007
16 (30.8)
27 (51.9)
9 (17.3)
21 (16.2)
65 (50.0)
44 (33.8)
35 (67.3)
17 (32.7)
61 (46.9)
69 (53.1)
21 (40.4)
14 (26.9)
7 (13.5)
3 (2.3)
52 (40.0)
52 (40.0)
.014
⬍.001
Fig. 2. Histopathology of case 2. This lesion exhibited the
histopathologic manifestation of melanotic macule (A) concomitant with melanoma (B). Hematoxylin-eosin staining.
Magnification ⫻100.
melanotic macule at the lower lip with no evidence of
malignancy (Fig. 3).
Fig. 1. Histopathology of case 1. Oral melanotic macule (A)
developed into melanoma (B). Hematoxylin-eosin staining.
Magnification ⫻100.
DISCUSSION
In this study, we attempted to investigate the clinical
features of oral melanotic macule and oral melanoma,
and assess the differences between the 2 groups.
Clinical features of the melanotic macule were generally similar to those found in other studies.3-5,17 We
observed oral melanotic macule mainly occurred in the
fifth decade of life, and more commonly in women
(M:F ratio 1:2.1), confirming the previously reported
female predilection. Lower lip and gingiva were the
most common sites. Few lesions were located on the
tongue, upper lip, or palate.
Studies on primary oral melanoma are scarce and
mostly reports of isolated cases or small-scale case
series.10-12,18-21 Sortino-Rachou et al.14 recently reported 28 cases of a total number of 319 patients with
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Shen et al.
Fig. 3. Histopathology of case 3. Oral melanotic macule (B)
had a previous melanoma (A). Hematoxylin-eosin staining.
Magnification ⫻100.
oral melanoma in the period of 1998-2002 from Asia,
using the Cancer Incidence in Five Continents Volume
IX database. Here, we documented 130 new patients
with oral melanoma in a hospital-based study from
China, one of the largest series of primary oral melanoma. Clinical characteristics shown in our series are
mostly consistent with other reports in the literature.812,18-23 We observed that oral melanoma mainly occurred after the fifth decade of life. Neonatal and infant
cases are rare, although we identified a 3-year-old patient and Sortino-Rachou et al. reported a 4-month-old
patient.14 We found no significant gender predilection
(M:F ratio 1.1:1). Earlier reports also suggested no or
minimal gender predilection.18,22,23 Palate and gingiva
were the most common sites. Few lesions were identified on the tongue, mandible, or lip.
Overall, we found significant differences in the age,
age group, gender, and site of lesions between oral
melanotic macule and primary oral malignant melanoma. At present, biopsy for routine histopathologic
examination is recommended to exclude melanoma
from oral pigmentations. For male patients ⬎60 years
old suspected of melanotic macule with lesion on the
palate, we further recommended routine biopsy to rule
out oral melanoma from these patients with melanotic
macule. These patients usually have a low incidence for
melanotic macule but a high incidence for melanoma.
In our analysis, we noted 3 cases with apparent
association between oral melanotic macule and melanoma. In the published literature, de Giorgi et al.24
reported 1 patient with oral melanotic macule who also
had a previous melanoma, and Kahn et al.2 reported an
oral melanotic macule developing into melanoma. Of
note, our case of oral melanotic macule developed into
melanoma within a 1-month time span at the same area
of the palate. Given the lack of precise data on the
biopsy site, we cannot rule out the possibility of sampling error. However, we also cannot confirm the benign nature of oral melanotic macule with no malignant
potential. Further studies are required to assess the
strength of the relationship. Although most oral melanoma arise de novo, from apparently normal mucosa, a
definite precursor lesion has not yet been identified.25
Single case reports of oral premalignant melanocytic
dysplasia and atypical melanocytic proliferation had
been observed.17,26
In our study, a patient with diagnosis of oral melanocytic nevus was excluded. Oral melanocytic nevus is
another type of benign pigmented lesions. Among 773
patients with biopsy-proven oral solitary melanocytic
lesions, Buchner et al.17 reported oral melanotic macules in 86.1% of patients and oral melanocytic nevi in
11.8% of patients. Meleti et al.16 presented an analysis
of 119 patients with oral melanocytic nevus, together
with a review of the literature, and concluded that their
evaluation did not provide concrete support for the idea
that the presence of an oral melanocytic nevus indicates
a risk of future melanoma transformation. Further studies are required to assess the entity of potential precursor lesions of oral melanoma.
In summary, the present paper was a retrospective
epidemiologic study from 1 center of oral melanotic
macule and melanoma. Significant differences in age,
gender, and location of lesions were observed between
the 2 groups. We observed association between oral
melanotic macule and melanoma in 3 cases, and we
recommend biopsy to rule out melanoma for male
patients ⬎60 years old with suspected melanotic macule lesion located on the palate.
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Reprint requests:
Zeng-Tong Zhou
Department of Oral Mucosal Diseases
Ninth People‘s Hospital
Shanghai Jiao Tong University School of Medicine
Shanghai Key Laboratory of Stomatology
Shanghai, China
[email protected]
Li-Zhen Wang
Department of Oral Pathology
Ninth People’s Hospital
Shanghai Jiao Tong University School of Medicine
Shanghai Key Laboratory of Stomatology
Shanghai, China
[email protected]